The Serie A powerhouse have appointed previous Italian national team manager the veteran manager to take the helm for the remainder of the campaign.
Spalletti takes over from Igor Tudor, who was dismissed following the loss to Lazio recently.
Tudor arrived at the club in March as Thiago Motta's replacement but departed after seven months after an eight-game winless streak.
Spalletti led Napoli to the Serie A title in 2022-23 before taking charge of Italy, who had failed to qualify for the 2022 World Cup with Mancini at the helm.
He secured their spot in Euro 2024 where they were knocked out in the last 16 by Switzerland.
Yet, the Italian FA let Spalletti go in June following a loss to Norway in World Cup qualifying, with the Azzurri at risk of missing out on a third consecutive World Cup.
He has previously coached Inter Milan, Roma, and Udinese in Italy's top flight and secured two Russian Premier League titles with Zenit St Petersburg.
Juventus were temporarily led by Massimo Brambilla during the 3-1 victory over Udinese on Wednesday which left them seventh in Serie A - six points behind leaders Napoli after nine games.
They are 25th in the league phase of the Champions League, having lost once and drawn twice in their opening three matches.